Publications by authors named "Aiping Zhao"

51 Publications

The Contributions of Language Skills and Comprehension Monitoring to Chinese Reading Comprehension: A Longitudinal Investigation.

Front Psychol 2021 19;12:625555. Epub 2021 Mar 19.

Department of Curriculum and Instruction, University of Huston, Houston, TX, United States.

This study examined how vocabulary, syntactic knowledge, and orthographic knowledge are related to comprehension monitoring and whether comprehension monitoring mediates the relations between these language skills and reading comprehension. Eighty-nine Chinese children were assessed on their vocabulary, syntactic knowledge, orthographic knowledge, and comprehension monitoring in Grade 1. Their reading comprehension skills were assessed in Grade 1 and Grade 3. Results showed that in Grade 1, comprehension monitoring mediated the relations between vocabulary and syntactic knowledge and reading comprehension. For Grade 3 reading comprehension, syntactic knowledge in Grade 1 was the only significant predictor. These findings indicate that multiple language skills make direct and indirect contributions comprehension monitoring to Chinese reading comprehension, and the relations would change as children's reading skills develop.
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http://dx.doi.org/10.3389/fpsyg.2021.625555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017195PMC
March 2021

Clinical characteristics, rates of blindness, and geographic features of PACD in China.

Can J Ophthalmol 2021 Jan 21. Epub 2021 Jan 21.

The Eye Hospital of Wenzhou Medical University, Wenzhou, China.

Objective: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China.

Methods: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed.

Results: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes.

Conclusion: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.
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http://dx.doi.org/10.1016/j.jcjo.2020.12.010DOI Listing
January 2021

The Chinese Glaucoma Study Consortium for Patients With Glaucoma: Design, Rationale and Baseline Patient Characteristics.

J Glaucoma 2019 11;28(11):974-978

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University.

Precis: Chinese Glaucoma Study Consortium (CGSC) as the first nationwide glaucoma registry in China, we describe its design, rationale, the geographic distribution of the hospitals, and baseline patient characteristics.

Aim: As a leading cause of blindness in China, glaucoma affects 2% to 4% of adults over the age of 40 and will become increasingly prevalent as the population ages. At the national level, there are few reports on the current medical practice for glaucoma patients. CGSC will be considered as the first nationwide glaucoma registry in China. Here we describe its design, rationale, the geographic distribution of the hospitals, and baseline patient characteristics.

Methods: From December 21, 2015 to September 9, 2018, CGSC recruited patients with the diagnoses of primary angle-closure suspect, primary angle-closure, primary angle-closure glaucoma, acute primary angle closure, primary open-angle glaucoma (POAG), pigmentary glaucoma (PG), and pseudoexfoliative glaucoma (PXG) from 111 hospitals covering 67 cities from 22 provinces, 4 municipalities, and 5 autonomous regions in mainland China. Clinical data were collected using an Electronic Data Capture System designed by Tongren hospital and Gauss informed Ltd. Blood samples were collected from every patient for further genetic analysis.

Results: Medical records of 10,892 patients were collected, of which 5762 patients have complete information. The average age of those with complete information (n=5762) was 62.05±11.26 years old, and 35.25% were males. Primary angle-closure disease, including primary angle-closure suspect/primary angle-closure/primary angle-closure glaucoma/acute primary angle closure, was predominant (4588, 79.63%), and the distribution for others is as follows: POAG (1116, 19.37%), PXG (41, 0.71%) and PG (17, 0.30%). A total of 16,684 blood samples were collected, of which 9917 (82.68%) were primary angle-closure disease, 1987 (16.57%) were POAG, 69 (0.58%) were PXG, 22 (0.18%) were PG, and 4689 were normal controls.

Conclusions: The CGSC is the first national-level glaucoma registry study in China. Clinical data and blood samples will provide the opportunity to study the epidemiology of glaucoma in Chinese hospitals, to evaluate the level of medical diagnosis and treatment of glaucoma in China, and to identify the susceptibility loci for glaucoma.
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http://dx.doi.org/10.1097/IJG.0000000000001378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028307PMC
November 2019

Inhibitory Effect of Protease Inhibitors on Larval Midgut Protease Activities and the Performance of (Lepidoptera: Plutellidae).

Front Physiol 2018 15;9:1963. Epub 2019 Jan 15.

Key Laboratory of Plant Protection Resources and Pest Management, Ministry of Education, Northwest A&F University, Yangling, China.

L. (diamondback moth) is a pest of cruciferous plants. To understand the relationship among protease inhibitors, protease activities and the growth and development of this insect, the activities of midgut proteases of larvae were determined in this study. Protease samples were extracted from the midguts of larvae, and the protease activities were determined using enzyme specific substrates. The results showed that CaCl, EDTA, and EGTA inhibited only the trypsin. Among the common protease inhibitors, phenylmethyl sulfonyl fluorine (PMSF), Nα-p-methyl sulfonyl-L-lysine chloromethylketone (TLCK), Nα-methyl sulfonyl-L- phenylalanine chloromethyl ketone (TPCK), soybean trypsin inhibitor (STI), and PMSF inhibited the total protease, high-alkaline trypsin (a trypsin subtype with highly alkaline pH optimum), low-alkaline trypsin (another trypsin subtype with slightly alkaline pH optimum), and chymotrypsin; TLCK inhibited the total protease and high-alkaline trypsin, whereas TPCK only activated the high-alkaline trypsin activities. STI had an inhibitory effect on all the proteases. These results showed that protease inhibitors had a certain extent inhibition to protease activities in the larval midgut of and that STI can potentially be used for effective pest control. The development of was delayed in the presence of different inhibitors. These effects were also related to the concentration of the inhibitor. A higher STI concentration showed a longer lasting effect but lower effect in this study compared to that of TLCK. The protease inhibitors had some inhibitory effect on the synthesis and secretion of proteases, and interfered with the protease activity, thereby inhibiting the absorption of nutrients and delaying the growth and development of and reducing their ability to reproduce. These findings should provide the baseline information about using for effective pest management in the future.
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http://dx.doi.org/10.3389/fphys.2018.01963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340996PMC
January 2019

Bone marrow PD-1 positive T cells reflect tumor mass and prognosis in multiple myeloma.

Int J Clin Exp Pathol 2018 1;11(1):304-313. Epub 2018 Jan 1.

Department of Hematology, The Second Hospital of Shandong University Jinan 250033, China.

Programmed cell death protein 1 (PD-1) negatively regulates T cell effector mechanisms and contributes to tumor cell escape from immune surveillance. To evaluate potential clinical significance of PD-1 in multiple myeloma (MM), we quantified PD-1 expressing T cells in bone marrow (BM) of MM patients using flow cytometry. Our results showed that PD-1 positive T cells in BM from relapsed/refractory patients were significantly higher than those in the newly diagnosed, partial/complete remission MM, and controls, respectively. Additionally, high-risk MM patients had more PD-1 positive T cells in BM than low-risk patients. Moreover, PD-1 positive T cells in relapsed/refractory MM patients were positively associated with myeloma cell counts in BM and clinical stages. PD-1 positive T cells in BM of all MM and relapsed/refractory MM patients were positively correlated with their serum β2-microglobulin concentrations. Our results strongly suggest that PD-1 expressing T cells in BM may be applied as a biomarker to reflect tumor mass and prognosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957957PMC
January 2018

Burden of vision loss associated with eye disease in China 19902020: findings from the Global Burden of Disease Study 2015.

Br J Ophthalmol 2018 02 12;102(2):220-224. Epub 2017 Jun 12.

Beijing Institute of Ophthalmology, Beijing, China.

Aims: To assess the burden of vision loss due to eye disease in China between 1990 and 2015, and to predict the burden in 2020.

Methods: Data from the GBD 2015 (Global Burden of Diseases, Injuries, and Risk Factors Study 2015) were used. The main outcome measures were prevalence and years lived with disability (YLDs) for vision loss due to cataract, glaucoma, macular degeneration, other vision loss, refraction and accommodation disorders and trachoma.

Results: Prevalence for eye diseases increased steadily from 1990 to 2015, and will increase until 2020. From 1990 to 2015, the most common eye disorder was refraction and accommodation disorders. From 1990 to 2015, the vision loss burden due to eye disease decreased for those aged 0-14 years, and increased for those aged 15 years and above, with the most notable increases occurring among those aged 50 years and above. China ranked 10th when comparing YLDs for vision loss due to eye disease with the other members of the G20 (Group of Twenty, an international forum for the governments from 20 major economies) . Age-standardised YLD rates for vision loss due to eye disease declined in all 19 countries, except for China. The burden from vision loss due to eye disease ranked 12th and 11th among all causes of health loss in China in 1990 and 2015, respectively.

Conclusion: Alone among major economies, China has experienced an increase in the burden of age-standardised vision loss from eye disease over the last two decades. In the future, China may expect a growing burden of vision loss due to population growth and ageing.
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http://dx.doi.org/10.1136/bjophthalmol-2017-310333DOI Listing
February 2018

IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity.

Cell Mol Immunol 2018 May 13;15(5):493-505. Epub 2017 Feb 13.

Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr-/-) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD). To observe the role of IL-25 in lipid metabolism, model mice were administered with IL-25 or adoptively transferred with IL-25-educated macrophages in vivo, whereas bone marrow-derived macrophages, the macrophage cell line RAW264.7 and adipocytes differentiated from 3T3-L1 were used in vitro. IL-25 was decreased in NAFLD patients and obese mice. In addition, IL-25 reduced body weight gain and lipid accumulation, enhanced lipid uptake by macrophages and increased the expression of lipolysis and β-oxidation enzymes via alternatively activating macrophages. IL-25 also promoted lipolysis and suppressed lipogenesis in adipocytes co-cultured with the IL-25-educated macrophages. Furthermore, IL-25 improved the mitochondrial respiratory capacity and oxygen consumption rate of macrophages and produced more NAD/NADH and ATP. In conclusion, IL-25 can stimulate M2 macrophage polarization and thereby promote lipolysis and mitochondrial respiratory capacity, highlighting the potential for IL-25 to be used as a therapeutic agent against obesity and associated metabolic syndromes.
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http://dx.doi.org/10.1038/cmi.2016.71DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068125PMC
May 2018

Critical Role for Interleukin-25 in Host Protective Th2 Memory Response against Heligmosomoides polygyrus bakeri.

Infect Immun 2016 Dec 18;84(12):3328-3337. Epub 2016 Nov 18.

Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China

Infection with parasitic nematodes, especially gastrointestinal geohelminths, affects hundreds of millions of people worldwide and thus poses a major risk to global health. The host mechanism of defense against enteric nematode infection remains to be fully understood, but it involves a polarized type 2 immunity leading to alterations in intestinal function that facilitate worm expulsion. We investigated the role of interleukin-25 (IL-25) in host protection against Heligmosomoides polygyrus bakeri infection in mice. Our results showed that Il25 and its receptor subunit, Il17rb, were upregulated during a primary infection and a secondary challenge infection with H. polygyrus bakeri Genetic deletion of IL-25 (IL-25) led to an attenuated type 2 cytokine response and increased worm fecundity in mice with a primary H. polygyrus bakeri infection. In addition, the full spectrum of the host memory response against a secondary infection with H. polygyrus bakeri was severely impaired in IL-25 mice, including delayed type 2 cytokine responses, an attenuated functional response of the intestinal smooth muscle and epithelium, diminished intestinal smooth muscle hypertrophy/hyperplasia, and impaired worm expulsion. Furthermore, exogenous administration of IL-25 restored the host protective memory response against H. polygyrus bakeri infection in IL-25 mice. These data demonstrate that IL-25 is critical for host protective immunity against H. polygyrus bakeri infection, highlighting its potential application as a therapeutic agent against parasitic nematode infection worldwide.
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http://dx.doi.org/10.1128/IAI.00180-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116711PMC
December 2016

Mechanisms Involved in the Development of the Chronic Gastrointestinal Syndrome in Nonhuman Primates after Total-Body Irradiation with Bone Marrow Shielding.

Radiat Res 2016 06 25;185(6):591-603. Epub 2016 May 25.

a   Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland;

In this study, nonhuman primates (NHPs) exposed to lethal doses of total body irradiation (TBI) within the gastrointestinal (GI) acute radiation syndrome range, sparing ∼5% of bone marrow (TBI-BM5), were used to evaluate the mechanisms involved in development of the chronic GI syndrome. TBI increased mucosal permeability in the jejunum (12-14 Gy) and proximal colon (13-14 Gy). TBI-BM5 also impaired mucosal barrier function at doses ranging from 10-12.5 Gy in both small intestine and colon. Timed necropsies of NHPs at 6-180 days after 10 Gy TBI-BM5 showed that changes in small intestine preceded those in the colon. Chronic GI syndrome in NHPs is characterized by continued weight loss and intermittent GI syndrome symptoms. There was a long-lasting decrease in jejunal glucose absorption coincident with reduced expression of the sodium-linked glucose transporter. The small intestine and colon showed a modest upregulation of several different pro-inflammatory mediators such as NOS-2. The persistent inflammation in the post-TBI-BM5 period was associated with a long-lasting impairment of mucosal restitution and a reduced expression of intestinal and serum levels of alkaline phosphatase (ALP). Mucosal healing in the postirradiation period is dependent on sparing of stem cell crypts and maturation of crypt cells into appropriate phenotypes. At 30 days after 10 Gy TBI-BM5, there was a significant downregulation in the gene and protein expression of the stem cell marker Lgr5 but no change in the gene expression of enterocyte or enteroendocrine lineage markers. These data indicate that even a threshold dose of 10 Gy TBI-BM5 induces a persistent impairment of both mucosal barrier function and restitution in the GI tract and that ALP may serve as a biomarker for these events. These findings have important therapeutic implications for the design of medical countermeasures.
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http://dx.doi.org/10.1667/RR14024.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966619PMC
June 2016

Type 3 muscarinic receptors contribute to intestinal mucosal homeostasis and clearance of Nippostrongylus brasiliensis through induction of TH2 cytokines.

Am J Physiol Gastrointest Liver Physiol 2016 07 12;311(1):G130-41. Epub 2016 May 12.

Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland

Despite increased appreciation for the role of nicotinic receptors in the modulation of and response to inflammation, the contribution of muscarinic receptors to mucosal homeostasis, clearance of enteric pathogens, and modulation of immune cell function remains relatively undefined. Uninfected and Nippostrongylus brasiliensis-infected wild-type and type 3 muscarinic receptor (M3R)-deficient (Chrm3(-/-)) mice were studied to determine the contribution of M3R to mucosal homeostasis as well as host defense against the TH2-eliciting enteric nematode N. brasiliensis Intestinal permeability and expression of TH1/TH17 cytokines were increased in uninfected Chrm3(-/-) small intestine. Notably, in Chrm3(-/-) mice infected with N. brasiliensis, small intestinal upregulation of TH2 cytokines was attenuated and nematode clearance was delayed. In Chrm3(-/-) mice, TH2-dependent changes in small intestinal function including smooth muscle hypercontractility, increased epithelial permeability, decreased epithelial secretion and absorption, and goblet cell expansion were absent despite N. brasiliensis infection. These findings identify an important role for M3R in host defense and clearance of N. brasiliensis, and support the expanding role of cholinergic muscarinic receptors in maintaining mucosal homeostasis.
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http://dx.doi.org/10.1152/ajpgi.00461.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967171PMC
July 2016

Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance.

Infect Immun 2016 Apr 24;84(4):1032-1044. Epub 2016 Mar 24.

Departments of Radiation Oncology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA

Nematode infection upregulates interleukin-4 (IL-4) and IL-13 and induces STAT6-dependent changes in gut function that promote worm clearance. IL-4 and IL-13 activate the type 2 IL-4 receptor (IL-4R), which contains the IL-13Rα1 and IL-4Rα chains. We used mice deficient in IL-13Rα1 (IL-13Rα1(-/-)) to examine the contribution of IL-13 acting at the type 2 IL-4R to immune and functional responses to primary (Hb1) and secondary (Hb2) infections with the gastrointestinal nematode parasite Heligmosomoides bakeri There were differences between strains in the IL-4 and IL-13 expression responses to Hb1 but not Hb2 infection. Following Hb2 infection, deficient mice had impaired worm expulsion and higher worm fecundity despite normal production of Th2-derived cytokines. The upregulation of IL-25 and IL-13Rα2 in Hb1- and Hb2-infected wild-type (WT) mice was absent in IL-13Rα1(-/-)mice. Goblet cell numbers and resistin-like molecule beta (RELM-β) expression were attenuated significantly in IL-13Rα1(-/-)mice following Hb2 infections. IL-13Rα1 contributes to the development of alternatively activated macrophages, but the type 1 IL-4R is also important. Hb1 infection had no effects on smooth muscle function or epithelial permeability in either strain, while the enhanced mucosal permeability and changes in smooth muscle function and morphology observed in response to Hb2 infection in WT mice were absent in IL-13Rα1(-/-)mice. Notably, the contribution of claudin-2, which has been linked to IL-13, does not mediate the increased mucosal permeability following Hb2 infection. These results show that activation of IL-13Rα1 is critical for key aspects of the immune and functional responses to Hb2 infection that facilitate expulsion.
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http://dx.doi.org/10.1128/IAI.00990-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807467PMC
April 2016

Functional synergism of Human Defensin 5 and Human Defensin 6.

Biochem Biophys Res Commun 2015 Nov 17;467(4):967-72. Epub 2015 Oct 17.

Institute of Human Virology and Department of Molecular Biology & Biochemistry of the University of Maryland Baltimore School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA. Electronic address:

The gut epithelium is critically involved in maintaining intestinal immune homeostasis. Acting as a physical barrier, it separates the intestinal microflora from cells of the immune system. In addition to its barrier function, the intestinal epithelium expresses defensins, natural, endogenous antimicrobial peptides. In humans, specialized epithelial cells, termed Paneth cells, located primarily in the small intestine express two defensins, Human Defensin-5 (HD-5) and Human Defensin-6 (HD-6). Previously, we have shown that HD-5 potently kills bacteria and induces secretion of interleukin-8 by intestinal epithelial cells. We show that HD-6 specifically and synergistically enhances the HD-5-induced IL-8 secretion, but does not alter its anti-bacterial activity. Further, we find that HD-5 decreases the trans-epithelial electrical resistance of intestinal epithelial cells and that HD-6 negates this effect of HD-5.
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http://dx.doi.org/10.1016/j.bbrc.2015.10.035DOI Listing
November 2015

IL-25 or IL-17E Protects against High-Fat Diet-Induced Hepatic Steatosis in Mice Dependent upon IL-13 Activation of STAT6.

J Immunol 2015 Nov 30;195(10):4771-80. Epub 2015 Sep 30.

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201;

IL-25 or IL-17E is a member of IL-17 cytokine family and has immune-modulating activities. The role of IL-25 in maintaining lipid metabolic homeostasis remains unknown. We investigated the effects of exogenous IL-25 or deficiency of IL-25 on hepatic lipid accumulation. IL-25 expression was examined in paraffin-embedded tissue sections of liver from patients or in the livers from mice. Mouse model of steatosis was induced by feeding a high-fat diet (HFD). Extent of steatosis as well as expression of cytokines, key enzymes for lipid metabolic pathways, markers for Kupffer cells/macrophages, and lipid droplet (LD) proteins, were analyzed. Our results show that hepatic steatosis in mice was accompanied by increased LD proteins, but decreased IL-25 in the liver. Decreased hepatic IL-25 was also observed in patients with fatty liver. Administration of IL-25 to HFD-fed wild-type mice led to a significant improvement in hepatic steatosis. This effect was associated with increased expression of IL-13, development of alternatively activated Kupffer cells/macrophages, and decreased expression of LD proteins in the liver. In contrast, administration of IL-25 to HFD-fed mice deficient in STAT6 or IL-13 had no effects. In addition, stimulation of primary hepatocytes with IL-13, but not IL-25, resulted in downregulation of LD proteins. Finally, mice deficient in IL-25 had exacerbated hepatic lipid accumulation when fed the HFD. These data demonstrate that dysregulated IL-25 expression contributes to lipid accumulation, whereas exogenous IL-25 protects against hepatic steatosis through IL-13 activation of STAT6. IL-25 and IL-13 are potential therapeutic agents for hepatic steatosis and associated pathologies.
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http://dx.doi.org/10.4049/jimmunol.1500337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637252PMC
November 2015

Type 2 immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis.

Microbiome 2015 Sep 17;3:40. Epub 2015 Sep 17.

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Dynamic interactions between the host and gastrointestinal microbiota play an important role for local and systemic immune homeostasis. Helminthic parasites modulate the host immune response, resulting in protection against autoimmune disease but also increased susceptibility to pathogen infection. The underlying mechanisms remain largely unknown.

Results: We showed that the type 2 immune response to enteric Nippostrongylus brasiliensis infection in mice was associated with altered intestinal mucin and AMP expression and shifts in microbiota composition. Most strikingly, infection reduced concentrations of intestinal segmented filamentous bacteria (SFB), known inducers of T helper 17 cells, and IL-17-associated gene expression. Infected mice deficient in IL-13 or STAT6 did not reduce SFB or IL-17, and exogenous IL-25 replicated the effects of parasite infection in wild type mice.

Conclusions: Our data show that parasite infection acts through host type 2 immunity to reduce intestinal SFB and expression of IL-17, providing an example of a microbiota-dependent immune modulation by parasites.
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http://dx.doi.org/10.1186/s40168-015-0103-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574229PMC
September 2015

Enteric nematodes and the path to up-regulation of type 2 cytokines IL-4 and IL-13.

Cytokine 2015 Sep 15;75(1):62-7. Epub 2015 Jul 15.

Dept. of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Dept. of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States.

Protective immunity against enteric parasitic nematodes is dependent on IL-4, IL-13 activation of their exclusive transcription factor STAT6. The precise pathways by which enteric parasitic nematodes are recognized by the host is unclear, but elimination of this important interaction in developed nations is thought to contribute to the dysregulated immune responses that are a characteristic of autoimmune diseases. Nematode-derived products are involved in evading host defenses to promote their life cycle leading to modulation of host immune responses. Host protective immunity has adapted to enteric parasitic nematode infection by elaboration of mucins, increasing intraluminal fluid to control access to the surface epithelium, increasing cell turnover to maintain an effective barrier to their invasion, initiating immune responses through activation of resident immune cells, and recruitment of additional immune cells to release immune mediators that help orchestrate these responses. Both the immune and functional outcomes depend largely on IL-4/IL-13 signaling through STAT6, with a dominant role for IL-13 working through the type 2 IL-4 receptor (IL-4R). The recent observation that enteric nematode infection prevents the onset of a number of experimental models of IBD, diabetes, and several extraintestinal autoimmune diseases including multiple sclerosis has generated considerable interest in the identification of worm/egg products involved in the generation and maintenance of Th2 cytokines that may mediate the beneficial effects of nematode infection in autoimmune and inflammatory pathologies.
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http://dx.doi.org/10.1016/j.cyto.2015.06.007DOI Listing
September 2015

Type 3 Muscarinic Receptors Contribute to Clearance of Citrobacter rodentium.

Inflamm Bowel Dis 2015 Aug;21(8):1860-71

*Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, Maryland; †United States Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland; ‡Department of Radiation Oncology, Division of Translational Radiation Sciences, University of Maryland School of Medicine, Baltimore, Maryland; and §Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.

Background: The role of muscarinic receptors in mucosal homeostasis, response to enteric pathogens, and modulation of immune cell function is undefined.

Methods: The contribution of type 3 muscarinic receptors (M3R) to mucosal homeostasis within the colon and host defense against Citrobacter rodentium was determined in uninfected and C. rodentium-infected WT and M3R-deficient (Chrm3) mice. In addition, WT and Chrm3 bone marrow-derived macrophages were studied to determine the ability of M3R to modulate macrophage phenotype and function.

Results: In Chrm3 mice, clearance of C. rodentium was delayed despite an amplified TH1/TH17 response. Delayed clearance of C. rodentium from Chrm3 mice was associated with prolonged adherence of bacteria to colonic mucosa, decreased goblet cell number, and decreased mucin 2 gene expression. Treatment of bone marrow-derived macrophages with bethanechol, a muscarinic-selective agonist, induced a classically activated macrophage phenotype, which was dependent on M3R expression. Chrm3 bone marrow-derived macrophages retained their ability to attain a classically activated macrophage phenotype when treated with the TH1 cytokine IFN-γ.

Conclusions: In Chrm3 mice, mucin production is attenuated and is associated with prolonged adherence of C. rodentium to colonic mucosa. The immune response, as characterized by production of TH1/TH17 cytokines, in C. rodentium-infected Chrm3 mice is intact. In addition, M3R activity promotes the development of classically activated macrophages. Our data establish a role for M3R in host defense against C. rodentium through effects on goblet cell mucus production and in the modulation of macrophage phenotype and function.
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http://dx.doi.org/10.1097/MIB.0000000000000408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821008PMC
August 2015

SerpinB2 mediated regulation of macrophage function during enteric infection.

Gut Microbes 2014 Mar-Apr;5(2):254-8. Epub 2014 Feb 5.

Department of Physiology; University of Maryland School of Medicine; Baltimore, MD USA; Center for Vascular and Inflammatory Diseases; University of Maryland School of Medicine; Baltimore, MD USA.

Host defense is an orchestrated response involving changes in the expression of receptors and release of mediators from both immune and structural cells. There is a growing recognition of the important role of proteolytic pathways for the protective immune response to enteric pathogens. Enteric nematode infection induces a type 2 immune response with polarization of macrophages toward the alternatively activated phenotype (M2). The Th2 cytokines, IL-4, and IL-13, induce a STAT6-dependent upregulation of the expression of the protease inhibitor, serpinB2, which protects macrophages from apoptosis. M2 are critical to worm clearance and a novel role for serpinB2 is its regulation of the chemokine, CCL2, which is necessary for monocyte and/or macrophage influx into small intestine during infection. There is a growing list of factors including immune (LPS, Th2 cytokines) as well as hormonal (gastrin, 5-HT) that are linked to increased expression of serpinB2. Thus, serpinB2 represents an immune regulated factor that has multiple roles in the intestinal mucosa.
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http://dx.doi.org/10.4161/gmic.28093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063854PMC
February 2015

Role of macrophages in the altered epithelial function during a type 2 immune response induced by enteric nematode infection.

PLoS One 2014 23;9(1):e84763. Epub 2014 Jan 23.

Department of Medicine and Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

Parasitic enteric nematodes induce a type 2 immune response characterized by increased production of Th2 cytokines, IL-4 and IL-13, and recruitment of alternatively activated macrophages (M2) to the site of infection. Nematode infection is associated with changes in epithelial permeability and inhibition of sodium-linked glucose absorption, but the role of M2 in these effects is unknown. Clodronate-containing liposomes were administered prior to and during nematode infection to deplete macrophages and prevent the development of M2 in response to infection with Nippostrongylus brasiliensis. The inhibition of epithelial glucose absorption that is associated with nematode infection involved a macrophage-dependent reduction in SGLT1 activity, with no change in receptor expression, and a macrophage-independent down-regulation of GLUT2 expression. The reduced transport of glucose into the enterocyte is compensated partially by an up-regulation of the constitutive GLUT1 transporter consistent with stress-induced activation of HIF-1α. Thus, nematode infection results in a "lean" epithelial phenotype that features decreased SGLT1 activity, decreased expression of GLUT2 and an emergent dependence on GLUT1 for glucose uptake into the enterocyte. Macrophages do not play a role in enteric nematode infection-induced changes in epithelial barrier function. There is a greater contribution, however, of paracellular absorption of glucose to supply the energy demands of host resistance. These data provide further evidence of the ability of macrophages to alter glucose metabolism of neighboring cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084763PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900397PMC
November 2014

Genetic deletion of IL-25 (IL-17E) confers resistance to dextran sulfate sodium-induced colitis in mice.

Cell Biosci 2014 26;4:72. Epub 2014 Nov 26.

Departments of Radiation Oncology and Medicine, University of Maryland School of Medicine, 10 S. Pine Street, MSTF, Room 7-00D, Baltimore, MD 21201 USA.

Background: IL-25 is emerging as a key regulator of inflammation in the intestinal mucosa because of its ability to promote type 2 while suppressing Th1 and Th17 responses. Several previous studies reported inconsistent results on the role of exogenous IL-25 in development of colonic inflammation and none were performed in animals with a genetic deletion of IL-25. We investigated the contribution of endogenous IL-25 to DSS-induced colitis using mice deficient in IL-25.

Results: Mice were exposed to DSS in drinking water ad libitum either for seven days (acute) or for three cycles of seven days with DSS followed by 14 days without DSS (chronic) to induce colitis, respectively. The loss of body weight, appearance of diarrhea and bloody stools, and shortening of colon length were significantly less pronounced in IL-25(-/-) mice compared to WT mice after exposure to acute DSS. Histological examination showed that DSS-treated IL-25(-/-) mice had only mild inflammation in the colon, while severe inflammation developed in DSS-treated WT mice. A significant up-regulation of IL-33 was observed in acute DSS-treated WT but not in the IL-25(-/-) mice. There was significantly lower expression of pro-inflammatory cytokines in the colon of acute DSS-treated IL-25(-/-) compared to WT mice. IL-25(-/-) mice were also partially protected from chronic DSS challenge especially during the first 2 cycles of DSS exposure. In contrast to IL-25(-/-) mice, IL-13(-/-) mice were more susceptible to DSS-induced colitis. Finally, stimulation of T84 colonic epithelial cells with IL-25 up-regulated the expression of IL-33 and several pro-inflammatory cytokines.

Conclusions: These data indicate that endogenous IL-25 acts as a pro-inflammatory factor in DSS-induced colitis, which is unlikely to be mediated by IL-13 but possibly the induction of IL-33 and other pro-inflammatory mediators from colonic epithelial cells. The present study suggests that IL-25 may contribute to the pathogenesis of inflammatory bowel disease in at least a subgroup of patients.
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http://dx.doi.org/10.1186/2045-3701-4-72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417544PMC
May 2015

CANDIDATE GENES FOR LIMITING CHOLESTATIC INTESTINAL INJURY IDENTIFIED BY GENE EXPRESSION PROFILING.

Physiol Rep 2013 Sep;1(4)

Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.

The lack of bile flow from the liver into the intestine can have devastating complications including hepatic failure, sepsis and even death. This pathologic condition known as cholestasis can result from etiologies as diverse as total parenteral nutrition (TPN), hepatitis and pancreatic cancer. The intestinal injury associated with cholestasis has been shown to result in decreased intestinal resistance, increased bacterial translocation and increased endotoxemia. Anecdotal clinical evidence suggests a genetic predisposition to exaggerated injury. Recent animal research on two different strains of inbred mice demonstrating different rates of bacterial translocation with different mortality rates supports this premise. In this study, a microarray analysis of intestinal tissue following common bile duct ligation (CBDL) performed under general anesthesia on these same two strains of inbred mice was done with the goal of identifying the potential molecular mechanistic pathways responsible. Over 500 genes were increased more than 2.0 fold following CBDL. The most promising candidate genes included MUPs, Serpina1a and LCN-2. RT-PCR validated the microarray results for these candidate genes. In an experiment using differentiated intestinal epithelial cells, inhibition of MUP-1 by siRNA resulted in increased intestinal epithelial cell permeability. Diverse novel mechanisms involving the growth hormone pathway, the acute phase response and the innate immune response are thus potential avenues for limiting cholestatic intestinal injury. Changes in gene expression were at times found to be not only due to the CBDL but also due to the murine strain. Should further studies in cholestatic patients demonstrate inter-individual variability similar to what we have shown in mice, then a "personalized medicine" approach to cholestatic patients may become possible.
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http://dx.doi.org/10.1002/phy2.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808870PMC
September 2013

Gut microbiota, tight junction protein expression, intestinal resistance, bacterial translocation and mortality following cholestasis depend on the genetic background of the host.

Gut Microbes 2013 Jul-Aug;4(4):292-305. Epub 2013 Apr 15.

Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.

Failure of the intestinal barrier is a characteristic feature of cholestasis. We have previously observed higher mortality in C57BL/6J compared with A/J mice following common bile duct ligation (CBDL). We hypothesized the alteration in gut barrier function following cholestasis would vary by genetic background. Following one week of CBDL, jejunal TEER was significantly reduced in each ligated mouse compared with their sham counterparts; moreover, jejunal TEER was significantly lower in both sham and ligated C57BL/6J compared with sham and ligated A/J mice, respectively. Bacterial translocation to mesenteric lymph nodes was significantly increased in C57BL/6J mice vs. A/J mice. Four of 15 C57BL/6J mice were bacteremic; whereas, none of the 17 A/J mice were. Jejunal IFN-γ mRNA expression was significantly elevated in C57BL/6J compared with A/J mice. Western blot analysis demonstrated a significant decrease in occludin protein expression in C57BL/6J compared with A/J mice following both sham operation and CBDL. Only C57BL/6J mice demonstrated a marked decrease in ZO-1 protein expression following CBDL compared with shams. Pyrosequencing of the 16S rRNA gene in fecal samples showed a dysbiosis only in C57BL/6J mice following CBDL when compared with shams. This study provides evidence of strain differences in gut microbiota, tight junction protein expression, intestinal resistance and bacterial translocation which supports the notion of a genetic predisposition to exaggerated injury following cholestasis.
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http://dx.doi.org/10.4161/gmic.24706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744514PMC
December 2013

SerpinB2 is critical to Th2 immunity against enteric nematode infection.

J Immunol 2013 Jun 29;190(11):5779-87. Epub 2013 Apr 29.

Department of Medicine, Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

SerpinB2, a member of the serine protease inhibitor family, is expressed by macrophages and is significantly upregulated by inflammation. Recent studies implicated a role for SerpinB2 in the control of Th1 and Th2 immune responses, but the mechanisms of these effects are unknown. In this study, we used mice deficient in SerpinB2 (SerpinB2(-/-)) to investigate its role in the host response to the enteric nematode, Heligmosomoides bakeri. Nematode infection induced a STAT6-dependent increase in intestinal SerpinB2 expression. The H. bakeri-induced upregulation of IL-4 and IL-13 expression was attenuated in SerpinB2(-/-) mice coincident with an impaired worm clearance. In addition, lack of SerpinB2 in mice resulted in a loss of the H. bakeri-induced smooth muscle hypercontractility and a significant delay in infection-induced increase in mucosal permeability. Th2 immunity is generally linked to a CCL2-mediated increase in the infiltration of macrophages that develop into the alternatively activated phenotype (M2). In H. bakeri-infected SerpinB2(-/-) mice, there was an impaired infiltration and alternative activation of macrophages accompanied by a decrease in the intestinal CCL2 expression. Studies in macrophages isolated from SerpinB2(-/-) mice showed a reduced CCL2 expression, but normal M2 development, in response to stimulation of Th2 cytokines. These data demonstrate that the immune regulation of SerpinB2 expression plays a critical role in the development of Th2-mediated protective immunity against nematode infection by a mechanism involving CCL2 production and macrophage infiltration.
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http://dx.doi.org/10.4049/jimmunol.1200293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068334PMC
June 2013

Dissociation of endotoxin tolerance and differentiation of alternatively activated macrophages.

J Immunol 2013 May 29;190(9):4763-72. Epub 2013 Mar 29.

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Endotoxin tolerance is a complex phenomenon characterized primarily by decreased production of proinflammatory cytokines, chemokines, and other inflammatory mediators, whereas the expression of other genes are induced or unchanged. Endotoxin tolerance is induced by prior exposure of murine macrophages/human monocytes, experimental animals, or people to TLR ligands. Although recent studies reported a possible relationship between endotoxin tolerance and differentiation of alternatively activated macrophages (AA-MΦs or M2), we show in this study that LPS pretreatment of IL-4Rα(-/-) and STAT6(-/-) macrophages, which fail to develop into AA-MΦs, resulted in tolerance of proinflammatory cytokines, as well as molecules and chemokines previously associated with AA-MΦs (e.g., arginase-1, mannose receptor, CCL2, CCL17, and CCL22). In contrast to LPS, wild-type (WT) MΦs pretreated with IL-4, the prototype inducer of AA-MΦs, did not induce endotoxin tolerance with respect to proinflammatory cytokines, AA-MΦ-associated chemokines, negative regulators, NF-κB binding and subunit composition, and MAPKs; conversely, IL-13(-/-) macrophages were tolerized equivalently to WT MΦs by LPS pretreatment. Further, IL-4Rα deficiency did not affect the reversal of endotoxin tolerance exerted by the histone deacetylase inhibitor trichostatin A. Like WT mice, 100% of LPS-tolerized IL-4Rα-deficient mice survived LPS + d-galactosamine-induced lethal toxicity and exhibited decreased serum levels of proinflammatory cytokines and AA-MΦ-associated chemokines induced by LPS challenge compared with nontolerized mice. These data indicate that the signaling pathways leading to endotoxin tolerance and differentiation of AA-MΦs are dissociable.
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http://dx.doi.org/10.4049/jimmunol.1202407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633613PMC
May 2013

Macrophages as IL-25/IL-33-responsive cells play an important role in the induction of type 2 immunity.

PLoS One 2013 25;8(3):e59441. Epub 2013 Mar 25.

Department of Medicine and the Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

Type 2 immunity is essential for host protection against nematode infection but is detrimental in allergic inflammation or asthma. There is a major research focus on the effector molecules and specific cell types involved in the initiation of type 2 immunity. Recent work has implicated an important role of epithelial-derived cytokines, IL-25 and IL-33, acting on innate immune cells that are believed to be the initial sources of type 2 cytokines IL-4/IL-5/IL-13. The identities of the cell types that mediate the effects of IL-25/IL-33, however, remain to be fully elucidated. In the present study, we demonstrate that macrophages as IL-25/IL-33-responsive cells play an important role in inducing type 2 immunity using both in vitro and in vivo approaches. Macrophages produced type 2 cytokines IL-5 and IL-13 in response to the stimulation of IL-25/IL-33 in vitro, or were the IL-13-producing cells in mice administrated with exogenous IL-33 or infected with Heligmosomoides bakeri. In addition, IL-33 induced alternative activation of macrophages primarily through autocrine IL-13 activating the IL-4Rα-STAT6 pathway. Moreover, depletion of macrophages attenuated the IL-25/IL-33-induced type 2 immunity in mice, while adoptive transfer of IL-33-activated macrophages into mice with a chronic Heligmosomoides bakeri infection induced worm expulsion accompanied by a potent type 2 protective immune response. Thus, macrophages represent a unique population of the innate immune cells pivotal to type 2 immunity and a potential therapeutic target in controlling type 2 immunity-mediated inflammatory pathologies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059441PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607614PMC
December 2013

Parasitic nematode-induced modulation of body weight and associated metabolic dysfunction in mouse models of obesity.

Infect Immun 2013 Jun 18;81(6):1905-14. Epub 2013 Mar 18.

Department of Medicine and the Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Obesity is associated with a chronic low-grade inflammation characterized by increased levels of proinflammatory cytokines that are implicated in disrupted metabolic homeostasis. Parasitic nematode infection induces a polarized Th2 cytokine response and has been explored to treat autoimmune diseases. We investigated the effects of nematode infection against obesity and the associated metabolic dysfunction. Infection of RIP2-Opa1KO mice or C57BL/6 mice fed a high-fat diet (HFD) with Nippostrongylus brasiliensis decreased weight gain and was associated with improved glucose metabolism. Infection of obese mice fed the HFD reduced body weight and adipose tissue mass, ameliorated hepatic steatosis associated with a decreased expression of key lipogenic enzymes/mediators, and improved glucose metabolism, accompanied by changes in the profile of metabolic hormones. The infection resulted in a phenotypic change in adipose tissue macrophages that was characterized by upregulation of alternative activation markers. Interleukin-13 (IL-13) activation of the STAT6 signaling pathway was required for the infection-induced attenuation of steatosis but not for improved glucose metabolism, whereas weight loss was attributed to both IL-13/STAT6-dependent and -independent mechanisms. Parasitic nematode infection has both preventive and therapeutic effects against the development of obesity and associated features of metabolic dysfunction in mice.
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http://dx.doi.org/10.1128/IAI.00053-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676010PMC
June 2013

IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent.

Am J Physiol Gastrointest Liver Physiol 2013 Feb 20;304(4):G381-9. Epub 2012 Dec 20.

Department of Medicine and the Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical "type 2" immune response in the gastrointestinal tract, yet the underlying mechanisms remain to be fully elucidated. In addition, the role of IL-33 in the regulation of gastrointestinal function is not known. The present study investigated IL-33-dependent intestinal immunity and function in mice. Exogenous IL-33 induced a polarized type 2 cytokine response in the intestine that was entirely MyD88 dependent but STAT6 and IL-13 independent. Mice injected with recombinant IL-33 exhibited intestinal smooth muscle hypercontractility, decreased epithelial responses to acetylcholine and glucose, and increased mucosal permeability. IL-33 effects on intestinal epithelial function were STAT6 dependent, and both IL-4 and IL-13 appeared to play a role. The effects on smooth muscle function, however, were attributable to both STAT6-dependent and -independent mechanisms. In addition, IL-13 induction of insulin-like growth factor-1 was implicated in IL-33-induced smooth muscle hypertrophy. Finally, alternative activation of macrophages induced by IL-33 revealed a novel pathway that is IL-4, IL-13, and STAT6 independent. Thus manipulating IL-33 or related signaling pathways represents a potential therapeutic strategy for treating inflammatory diseases associated with dysregulated intestinal function.
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http://dx.doi.org/10.1152/ajpgi.00357.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566613PMC
February 2013

Anti-Inflammatory Activities of a Chinese Herbal Formula IBS-20 In Vitro and In Vivo.

Evid Based Complement Alternat Med 2012 22;2012:491496. Epub 2012 Feb 22.

Department of Medicine and Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Irritable bowel syndrome (IBS) is a functional bowel disorder and the etiology is not well understood. Currently there is no cure for IBS and no existing medication induces symptom relief in all patients. IBS-20 is a 20-herb Chinese medicinal formula that offers beneficial effects in patients with IBS; however, the underlying mechanisms are largely unknown. This study showed that IBS-20 potently inhibited LPS- or IFNΓ-stimulated expression of pro-inflammatory cytokines, as well as classically activated macrophage marker nitric oxide synthase 2. Similarly, IBS-20 or the component herb Coptis chinensis decreased LPS-stimulated pro-inflammatory cytokine secretion from JAWS II dendritic cells. IBS-20 or the component herbs also blocked or attenuated the IFNΓ-induced drop in transepithelial electric resistance, an index of permeability, in fully differentiated Caco-2 monolayer. Finally, the up-regulation of key inflammatory cytokines in inflamed colon from TNBS-treated mice was suppressed significantly by orally administrated IBS-20, including IFNΓ and IL-12p40. These data indicate that the anti-inflammatory activities of IBS-20 may contribute to the beneficial effects of the herbal extract in patients with IBS, providing a potential mechanism of action for IBS-20. In addition, IBS-20 may be a potential therapeutic agent against other Th1-dominant gut pathologies such as inflammatory bowel disease.
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http://dx.doi.org/10.1155/2012/491496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296463PMC
August 2012

Simultaneous determination of free amino acid content in tea infusions by using high-performance liquid chromatography with fluorescence detection coupled with alternating penalty trilinear decomposition algorithm.

J Agric Food Chem 2011 Oct 28;59(20):10839-47. Epub 2011 Sep 28.

College of Chemistry, Sichuan University, Chengdu 610064, People's Republic of China.

In this paper, a novel application of alternating penalty trilinear decomposition (APTLD) for high-performance liquid chromatography with fluorescence detection (HPLC-FLD) has been developed to simultaneously determine the contents of free amino acids in tea. Although the spectra of amino acid derivatives were similar and a large number of water-soluble compounds are coextracted, APTLD could predict the accurate concentrations together with reasonable resolution of chromatographic and spectral profiles for the amino acids of interest owing to its "second-order advantage". An additional advantage of the proposed method is lower cost than traditional methods. The results indicate that it is an attractive alternative strategy for the routine resolution and quantification of amino acids in the presence of unknown interferences or when complete separation is not easily achieved.
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http://dx.doi.org/10.1021/jf2023325DOI Listing
October 2011

Enteric pathogens and gut function: Role of cytokines and STATs.

Gut Microbes 2010 Sep 12;1(5):316-324. Epub 2010 May 12.

Department of Medicine; University of Maryland School of Medicine, Baltimore, MD USA.

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against the pathogens. In response to the invasion of various pathogens, naïve CD4(+) cells differentiate into subsets of T helper (Th) cells that are characterized by different cytokine profiles. Cytokines bind to cell surface receptors on both immune and non-immune cells leading to activation of JAK-STAT signaling pathway and influence gut function by upregulating the expression of specific target genes. This review considers the roles of cytokines and receptor-mediated activation of STATs on pathogen-induced changes in gut function. The focus on STAT4 and STAT6 is because of their requirement for the full development of Th1 and Th2 cytokine profiles.
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http://dx.doi.org/10.4161/gmic.1.5.13329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023616PMC
September 2010
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